Monatsh Chem 139, 1363–1367 (2008) DOI 10.1007/s00706-008-0925-1 Printed in The Netherlands
Iodine as a mild, efficient, and cost-effective catalyst for the synthesis of thiiranes from oxiranes Jhillu S. Yadav, Basi V. Subba Reddy, Sandip Sengupta, Manoj K. Gupta, Gakul Baishya, Sukkala J. Harshavardhana, Uttam Dash Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad, India Received 26 October 2007; Accepted 27 February 2008; Published online 9 June 2008 # Springer-Verlag 2008
Abstract We developed an efficient protocol for the
synthesis of thiiranes from oxiranes using a catalytic amount of molecular iodine. The notable features of this procedure are mild reaction conditions, high conversions, short reaction times, economic viability of the reagents, compatibility with various functionalities, and simple experimental=product isolation procedures which make it a useful and attractive process for the synthesis of a range of thiiranes. Keywords Oxiranes; thiocyanate.
Thiiranes;
Iodine;
Ammonium
Introduction Thiiranes are important and useful building blocks for the synthesis of polymers, pharmaceuticals, pesticides, and herbicides [1]. Since organo-sulfur compounds have become increasingly useful and important in the field of drugs and pharmaceuticals, the development of simple, convenient and efficient approaches are desirable. As a result, numerous methods have been reported to synthesize thiiranes using a variety of reagents such as -cyclodextrin= thiourea [2], phosphine sulfide [3], N,N-dimethylthioformamide in the presence of trifluoroacetic acid Correspondence: Jhillu S. Yadav, Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India. E-mail:
[email protected]
[4], silica gel supported potassium thiocyanate [5], indium halides=KSCN [6] and polymeric cosolvent= NH4SCN [7], together with solvent-free conditions [8], ionic liquids [9], and several more [10, 11]. However, many of these methods often involve the use of expensive or toxic reagents, the formation of mixtures of products resulting in low yields, and undesirable side reactions due to the rearrangement or polymerization of the starting oxiranes. In spite of a number of methods reported for the synthesis of thiiranes, there is always a great demand in developing catalytic methods for high yielding protocols using readily available and less expensive reagents. Recently, molecular iodine has received considerable attention as an inexpensive, non-toxic, and readily available reagent for various organic transformations, affording the corresponding products with high selectivity in excellent yields [12–16]. The mild Lewis acidity associated with iodine has led to its use in organic synthesis using catalytic to stoichiometric amounts. However, there have been no reports on the use of iodine for the synthesis of thiiranes from oxiranes and ammonium thiocyante.
Scheme 1
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J. S. Yadav et al.
Table 1 Iodine catalyzed synthesis of thiiranes from oxiranes Time=h
Yield=%b
a
2.5
94
b
3.5
96
c
3.5
96
d
2.5
95
e
3.5
90
f
4.0
90
g
5.0
80
h
3.0
93
i
2.5
93
j
3.5
96
k
3.5
96
l
3.0
80
m
3.5
82
n
3.5
82
o
7.5
85
P
7.0
75
Entry
a b
Oxiiranes
Thiiranesa
All products were characterized by IR, 1H NMR spectra and mass spectrometry Isolated and unoptimized yields after column chromatography
Iodine as a mild, efficient, and cost-effective catalyst
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Results and discussion In continuation of our interest in the catalytic application of elemental iodine [17–19], we disclose herein a mild, efficient, and practical methodology for the synthesis of thiiranes from oxiranes and ammonium thiocyanate using molecular iodine as a catalyst. Initially, we attempted the reaction of 2(phenoxymethyl)oxirane (1, 1 eq.) with ammonium thiocyante (2, 1.5 eq.) in the presence of 10 mol% of elemental iodine in acetonitrile at room temperature. The reaction went to completion in 2.5 h affording thiirane 3a in 94% yield (Scheme 1). The remarkable catalytic activity of molecular iodine provided the incentive for further study of reactions with other epoxides. Interestingly, a variety of epoxides reacted efficiently with ammonium thiocyanate to furnish the corresponding thiiranes in good yields (entries b–p, Table 1). In addition, functionalized oxiranes also worked well under these reaction conditions without affecting the protecting groups (entries e, i–p, Table 1, Scheme 2). This method is compatible with substrates bearing acid sensitive protecting groups such as THP, TBDMS, benzyl, and methyl ethers (entries e, i–p, Table 1). This procedure is also useful for the selective conversion of an epoxide into a thiirane without affecting an acid labile primary acetonide (entry p, Table 1). The reaction may proceed via the activation of oxirane by I2 followed by nucleophilic ring opening with SCN and a subsequent formation of oxathiolanium intermediate, which eventually undergoes a rearrangement to thiirane (Scheme 3) [20]. However, most of the existing methods failed to produce thiiranes from oxiranes without the cleavage of THP, TBDMS ethers, and acetonide [1]. The products thus obtained were
Scheme 2
characterized by 1H NMR, IR, and mass spectrometry. In all cases, the reactions proceeded well in refluxing acetonitrile and the products were obtained in relatively high yields. To know the efficiency of elemental iodine, we have carried out the experiments with some reported catalysts and the comparative results are summarized in Table 2. The scope and generality of this process is illustrated in Table 1. Experimental Melting points were recorded on a Bu¨chi R-535 apparatus. IR spectra were recorded on a Perkin-Elmer FT-IR 240-c spectrophotometer using KBr optics. 1H NMR spectra were recorded on a Varian-unity 300 spectrometer in CDCl3 using TMS as internal standard. Mass spectra were recorded on a Finnigan MAT 1020 mass spectrometer operating at 70 eV. General procedure for the synthesis of thiiranes A mixture of 1 mmol oxiranes, 1.5 mmol ammonium thiocyanate, and 25 mg iodine (10 mol%) in 5 cm3 dry acetonitrile was stirred for a specified time (see Table 1). After completion of the reaction as indicated by TLC, the solvent was evaporated under vacuum and reaction mass was quenched with 2 cm3 sat. ammonium thiosulphate and extracted with 2 10 cm3 ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, concentrated in vacuo, and purified by column chromatography on silica gel (Merck, 100–200 mesh, ethyl acetate:n-hexane, 1:9) to afford pure thiiranes. The products thus obtained were characterized by their TLC, IR, NMR spectroscopy,
Scheme 3
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J. S. Yadav et al.
Table 2 A Comparative study for the synthesis of benzyloxymethylthiirane from benzyloxymethyloxirane S. Catalyst No. 1 2 3 4 5 6 7
Oxalic acid (0.2 eq) RuCl3 (0.05 eq) SiO2 –AlCl3 (0.1 eq) Al(DS)3 3H2O (0.1 eq) PVA and PAA=NaOH TiO(TFA)2 or TiCl3(OTf) Iodine (0.1 eq)
Conversion Time Yielda % h % 91 95 90 92 92 98 96
2.0 0.5 2.0 2.5 1.0 0.5 2.5
85 90 89 90 90 95 94
¼ 7.31–7.20 (m, 5H), 4.53 (d, J ¼ 0.9 Hz, 2H), 3.67 (ddd, J ¼ 10.3, 5.4, 0.7 Hz, 1H), 3.38 (dd, J ¼ 10.3, 6.7 Hz, 1H), 3.06–2.98 (m, 1H), 2.45 (td, J ¼ 6.2, 2.0, 0.9 Hz, 1H), 2.15 (dd, J ¼ 5.2, 1.1 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 32.5, 42.8, 71.8, 73.5, 127.9, 128.6, 130.1, 140.6 ppm; ESI=MS: m=z ¼ 181.0 [Mþ þ H], 102.1; HRMS (ESI): calcd for C10H12ONaS 203.0506, found 203.0509.
and mass spectrometry. Data for 3e, 3g, 3h, and 3i are identical with these in Refs. [2, 6, 21, 22].
2-Phenylthiirane (3f, C8H8S) Colorless liquid; IR (KBr): max ¼ 3061, 3029, 2924, 2852, 1492, 1453, 1071, 1040, 760, 695, 613 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.27–7.18 (m, 5H), 3.81 (t, J ¼ 6.5 Hz, 1H), 2.80 (d, J ¼ 6.5 Hz, 1H), 2.56 (dd, J ¼ 5.0, 1.4 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 35.2, 42.4, 125.1, 128.3, 130.2, 139.8 ppm; FAB Mass: m=z ¼ 137 [Mþ þ H], 136.0; HRMS (ESI): calcd for C8H8NaS 159.0245, found 159.0252.
2-(Phenoxymethyl)thiirane (3a, C9H10OS) Colorless liquid; IR (KBr): max ¼ 3034, 2925, 2860, 1599, 1495, 1241, 1036, 753 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.26–7.19 (m, 2H), 6.93–6.82 (m, 3H), 4.23 (dd, J ¼ 11.3, 6.4 Hz, 1H), 3.77 (dd, J ¼ 9.8, 7.5 Hz, 1H), 3.25–3.17 (m, 1H), 2.57 (dd, J ¼ 6.0, 1.5 Hz, 1H), 2.27 (d, J ¼ 6.0 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 23.9, 31.3, 72.5, 114.6, 121.1, 129.5, 158.3 ppm; ESI=MS: m=z ¼ 189.9 [Mþ þ Na], 117.2; HRMS (ESI): calcd for C9H10ONaS 189.0350, found 189.0359.
2-[2-(Benzyloxy)-2-phenylethyl]thiirane (3j, C17H18OS) Liquid; IR (KBr): max ¼ 3061, 3028, 2861, 1493, 1451, 1091, 783, 699 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.36–7.14 (m, 10H), 4.53–4.39 (m, 2H), 4.31–4.21 (dd, J ¼ 11.7, 8.8 Hz, 1H), 3.21–2.93 (m, 1H), 2.50–2.31 (m, 2H), 2.12–1.96 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 25.6, 31.9, 70.3, 81.2, 126.8, 127.6, 127.7, 127.9, 128.3, 128.5, 141.1, 141.6 ppm; ESI=MS: m=z ¼ 271 [Mþ þ H], 179.1; HRMS (ESI): calcd for C17H18ONaS 293.0976, found 293.0971.
2-[(2-Methylphenoxy)methyl]thiirane (3b, C10H12OS) Colorless liquid; IR (KBr): max ¼ 2922, 2858, 1494, 1460, 1242, 1120, 1047, 1011, 750 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.07 (t, J ¼ 7.5 Hz, 2H), 6.81 (t, J ¼ 7.5 Hz, 1H), 6.72 (d, J ¼ 8.3 Hz, 1H), 4.21 (dd, J ¼ 10.5, 5.2 Hz, 1H), 3.82 (dd, J ¼ 10.5, 7.5 Hz, 1H), 3.27–3.19 (m, 1H), 2.55 (d, J ¼ 6.0 Hz, 1H), 2.28 (dd, J ¼ 5.2, 1.5 Hz, 1H), 2.23 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 16.1, 23.7, 31.5, 72.5, 111.4, 120.8, 126.6, 126.9, 130.7, 156.4 ppm; ESI=MS: m=z ¼ 181 [Mþ þ H], 179; HRMS (ESI): calcd for C10H12ONaS 203.0506, found 203.0510.
2-[2-(Benzyloxy)-2-cyclohexylethyl]thiirane (3k, C17H24OS) Colorless liquid; IR (KBr): max ¼ 2925, 2852, 1449, 1098, 1068, 737, 697 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.42– 7.17 (m, 5H), 4.57 (d, J ¼ 3.6 Hz, 1H), 4.48 (s, 1H), 3.39–3.21 (m, 1H), 3.08–2.82 (m, 1H), 2.52 (d, J ¼ 6.6 Hz, 1H), 2.40 (d, J ¼ 5.8 Hz, 1H), 2.20–1.88 (m, 2H), 1.83–1.55 (m, 6H), 1.42– 0.93 (m, 5H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 26.3, 26.8, 28.6, 28.9, 34.0, 38.6, 41.4, 72.7, 83.3, 127.7, 127.8, 128.2, 138.8 ppm; ESI=MS: m=z ¼ 277 [Mþ þ H], 278.1; HRMS (ESI): calcd for C17H24ONaS 299.1445, found 299.1454.
2-[(2-Napthyloxy)methyl]thiirane (3c, C13H12OS) White solid; mp 72 C; IR (KBr): max ¼ 2923, 2854, 1627, 1595, 1463, 1389, 1256, 1216, 1182, 1045, 1005, 839, 813, 741 cm1 ; 1H NMR (CDCl3 300 MHz): ¼ 7.71–7.62 (m, 3H), 7.38 (t, J ¼ 7.5 Hz, 1H), 7.28 (t, J ¼ 8.3 Hz, 1H), 7.09 (dd, J ¼ 9.0, 2.2 Hz, 1H), 7.05 (d, J ¼ 2.2 Hz, 1H), 4.33 (dd, J ¼ 9.8, 5.2 Hz, 1H), 3.88 (dd, J ¼ 9.8, 7.5 Hz, 1H), 3.30– 3.22 (m, 1H), 2.58 (d, J ¼ 6.0 Hz, 1H), 2.30 (dd, J ¼ 5.2, 1.5 Hz, 1H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 23.9, 31.2, 72.4, 76.9, 106.8, 118.6, 123.7, 127.5, 129.0, 129.5, 134.3, 156.2 ppm; ESI=MS: m=z ¼ 217 [Mþ þ H], 197; HRMS (ESI): calcd for C13H12ONaS 239.0506, found 239.0512.
tert-Butyldimethyl(4-(thiiran-2-yl)butoxy)silane (3l, C12H26OSiS) Liquid; IR (KBr): max ¼ 2932, 2858, 2363, 1731, 1467, 1388, 1361, 1253, 1102, 1007, 837, 776, 662 cm1 . 1H NMR (CDCl3, 300 MHz): ¼ 3.63–3.59 (m, 2H), 2.81–2.77 (m, 1H), 2.43 (d, J ¼ 6.0 Hz, 1H), 2.08 (d, J ¼ 6.0 Hz, 1H), 1.86– 1.82 (m, 2H), 1.60–1.51 (m, 4H), 0.88 (s, 9H), 0.33 (s, 6H) ppm. ESI=MS: m=z ¼ 247 [Mþ þ H].
a
Yield refers to pure products after chromatography
2-[(Benzyloxy)methyl]thiirane (3d, C10H12OS) Liquid; IR (KBr): max ¼ 3028, 2923, 2855, 1452, 1368, 1249, 1092, 739, 697 cm1 ; 1H NMR (CDCl3, 300 MHz):
2-(4-(Thiiran-2-yl)butoxy)-tetrahydro-2H-pyran (3m, C11H20O2S) Liquid; IR (KBr): max ¼ 2925, 2853, 2366, 1742, 1458, 1370, 1167, 1121, 1026 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 4.56–4.51 (m, 1H), 3.84–3.77 (m, 1H), 3.73–3.67 (m, 1H), 3.50–3.41 (m, 1H), 3.38–331 (m, 1H), 2.88–2.81 (m, 1H), 2.46 (d, J ¼ 6.7 Hz, 1H), 2.11 (d, J ¼ 5.2 Hz, 1H), 1.92–1.76
Iodine as a mild, efficient, and cost-effective catalyst (m, 2H), 1.77–1.48 (m, 10H) ppm; ESI=MS: m=z ¼ 217 [Mþ þ H]. 2-[3-(Benzyloxy)propyl]thiirane (3n, C12H16OS) Colorless liquid; IR (KBr): max ¼ 2927, 2855, 1449, 1362, 1102, 740 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.31– 7.18 (m, 5H), 4.43 (s, 2H), 3.46 (dt, J ¼ 8.0, 5.8, 2.1 Hz, 2H), 2.86–2.74 (dt, J ¼ 7.3, 5.8, 2.1 Hz, 1H), 2.39 (d, J ¼ 6.5 Hz, 1H), 2.05 (d, J ¼ 6.5 Hz, 1H), 2.01–1.88 (m, 1H), 1.84–1.70 (m, 2H), 1.53–1.39 (m, 1H) ppm; 13C NMR (75 MHz, CDCl3): ¼ 35.6, 25.8, 29.3, 33.2, 69.4, 72.8, 128.2, 127.5, 127.4, 138.3 ppm; ESI=MS: m=z ¼ 231 [Mþ þ Na], 184.1; HRMS (ESI): calcd for C12H16ONaS 231.0819, found 231.0826. 2-[2-(Methoxy)-2-phenylethyl]thiirane (3o, C11H14OS) Liquid; IR (KBr): max ¼ 3061, 3027, 2983, 2930, 2856, 2821, 1453, 1356, 1237, 1191, 1100, 1048, 758, 701, 612, 561 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.35–7.21 (m, 5H), 4.27–4.18 (m, 1H), 3.23 (d, J ¼ 18.8 Hz, 3H), 3.14– 3.05 (m, 1H), 2.64–2.48 (m, 1H), 2.37–2.26 (m, 1H), 2.10– 2.01 (m, 2H) ppm; ESI=MS: m=z ¼ 217 [Mþ þ Na], 172, 74.1. 4-(1,2-bis(benzyloxy)-2-(thiiran-2-yl)ethyl)-2,2-dimethyl1,3-dioxolane (3p, C23H28O4S) Liquid; IR (KBr): max ¼ 3064, 3030, 2985, 2927, 1631, 1495, 1454, 1384, 1254, 1212, 1070, 856, 736, 698 cm1 ; 1H NMR (CDCl3, 300 MHz): ¼ 7.30–7.23 (m, 10H), 4.82–4.74 (m, 2H), 4.63–4.57 (m, 2H), 4.17 (dt, J ¼ 6.8, 4.5 Hz 1H), 3.97 (dt, J ¼ 12.8, 8.3 Hz, 2H), 3.76–3.69 (m, 1H), 3.02 (dd, J ¼ 8.3, 3.0 Hz, 1H), 2.95–2.88 (m, 1H), 2.09 (dd, J ¼ 6.0, 1.5 Hz, 1H), 1.95 (dd, J ¼ 5.2, 1.5 Hz, 1H), 1.39 (s, 3H), 1.29 (s, 3H) ppm; ESI=MS: m=z ¼ 423 [Mþ þ Na], 407.
Acknowledgements SS, MKG, GB, SJH, and UD thank CSIR, New Delhi, for the award of fellowships.
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